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Design, 2D Qsar Studies, Molecular Docking, and Synthesis of Novel Triazole Derivatives intended as an Antifungal Agents

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Abstract

Synthesis of a series of triazole derivatives involved the reaction of pyridine potassium dithiocarbazate and 4-amino-5-(pyridine-4-yl)-4H-1,2,4-triazole-3-thiols derivative in dimethylformamide, formaldehyde, and appropriate aniline. Subsequently, a QSAR model was created using QSARINS to investigate the structural requirements for antifungal activities against Candida albicans. The optimal model (Model 2) was determined, featuring variables such as SHaaCH, maxHBint2, ETA_Epsilon_5, and ETA_EtaP_B_RC, with statistical values R2: 0.9846, Q2loo: 0.9774, Q2LMO: 0.9751, CCC tr: 0.9922, and PRESS cv: 0.6456. To assess binding affinity, docking of all designed compounds was conducted in AutoDock Vina using PyRx.Ink, specifically targeting the active site of Cytosolic leucyl tRNA synthetase (PDB ID: 2WFG). Compounds exhibiting favorable binding affinity were then synthesized, characterized by FT-IR and mass spectroscopy. Antifungal activity assessment using the agar well diffusion method, with amphotericin B as the standard, revealed that compounds (IIIm), (IIIo), (IIIq), (IIIr), and (IIIu) exhibited excellent activity against Candida albicans, with zone of inhibition values of 11.25 ± 0.35, 13.25 ± 0.35, 12.25 ± 0.35, and 11.25 ± 0.35 mm (500 µg/mL), respectively, compared to the standard amphotericin B.

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DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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ACKNOWLEDGMENTS

The authors express gratitude to the management of C.L. Baid Metha College of Pharmacy, Thoraipakkam, Chennai, for providing the essential facilities to successfully conduct this work.

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This research does not receive any specific grant from funding agencies in the public, commercial or not-for-public sectors.

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Authors and Affiliations

  1. Department of Pharmaceutical Chemistry, C.L. Baid Metha College of Pharmacy, Tamil Nadu Dr. MGR. Medical University, Thoraipakkam, 600097, Chennai, India

    K. Yuvarani & N. Ramalakshmi

  2. School of Pharmacy, Sathyabama Institute of Science and Technology, Chennai, 600119, Tamil-Nadu, India

    S. Arunkumar

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  1. K. Yuvarani
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  2. N. Ramalakshmi
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  3. S. Arunkumar
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The authors NR and SA—selected the literature data on the review topic. The author KY—contributed to manuscript preparation. All authors participated in the discussions.

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Correspondence to K. Yuvarani.

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Yuvarani, K., Ramalakshmi, N. & Arunkumar, S. Design, 2D Qsar Studies, Molecular Docking, and Synthesis of Novel Triazole Derivatives intended as an Antifungal Agents. Russ J Bioorg Chem 49 (Suppl 1), S202–S223 (2023). https://doi.org/10.1134/S1068162023080198

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